ORCID Profile
0000-0002-1726-7700
Current Organisation
Saint James's Hospital
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Publisher: MDPI AG
Date: 09-10-2019
DOI: 10.3390/IJMS20204991
Abstract: (1) Background: Firm consensus has yet to be established in relation to taxonomic classification and primer choice in targeted licon sequencing of the mycobiome. While the nuclear ribosomal internal transcribed spacer (ITS) region are recognized as the formal fungal taxonomic barcode, appraisal of different ITS sub-regions and the influence of DNA extraction methods have not been comprehensively undertaken using human respiratory specimens. (2) Methods: We performed ITS analysis of respiratory (sputum) s les by assessing (a) the effect of alternate DNA extraction techniques and (b) an evaluation of four different ITS primer pairs (ITS1F and ITS2 ITS1-30F and ITS1-217R gITS7ngs and ITS4ng and Fseq and Rseq) on the mycobiome profiles generated for mock fungal communities and their respective clinical (airway) specimens. (3) Results: Primer pairs varied in their resulting ITS mycobiome profiles, suggesting that particular pairs may be more relevant for analysis of respiratory s les compared to others. Assessment of DNA extraction methods highlighted lower final DNA concentrations achieved by mechanical disruption compared to enzymatic lysis. However, despite lower yields, DNA liberated by mechanical lysis more readily yielded ITS bands with highest success in combination with the Fseq and Rseq primers. (4) Conclusion: Choice of extraction method, primers used, and sequencing approach are all important considerations in sequencing the mycobiome and should be tailored to s le type. A standardization of approach to mycobiome studies using respiratory specimens will permit more reliable comparisons between studies and improve our understanding of the role of fungi in the human airway.
Publisher: American Society for Microbiology
Date: 02-11-2017
Abstract: The spread of multidrug-resistant (MDR) tuberculosis (TB) has become a major global challenge. In 2016, Tasmania recorded its first known incidence of MDR-TB. Here, we report the draft whole-genome sequence of the Mycobacterium tuberculosis isolate from this case, TASMDR1, and describe single-nucleotide polymorphisms associated with its drug resistance.
Publisher: Wiley
Date: 19-01-2017
DOI: 10.1111/RESP.12971
Abstract: There is currently enormous interest in studying the role of the microbiome in health and disease. Microbiome's role is increasingly being applied to respiratory diseases, in particular COPD, asthma, cystic fibrosis and bronchiectasis. The changes in respiratory microbiomes that occur in these diseases and how they are modified by environmental challenges such as cigarette smoke, air pollution and infection are being elucidated. There is also emerging evidence that gut microbiomes play a role in lung diseases through the modulation of systemic immune responses and can be modified by diet and antibiotic treatment. There are issues that are particular to the Asia-Pacific region involving diet and prevalence of specific respiratory diseases. Each of these issues is further complicated by the effects of ageing. The challenges now are to elucidate the cause and effect relationships between changes in microbiomes and respiratory diseases and how to translate these into new treatments and clinical care. Here we review the current understanding and progression in these areas.
Publisher: Springer Science and Business Media LLC
Date: 04-2021
DOI: 10.1038/S41591-021-01289-7
Abstract: Bronchiectasis, a progressive chronic airway disease, is characterized by microbial colonization and infection. We present an approach to the multi-biome that integrates bacterial, viral and fungal communities in bronchiectasis through weighted similarity network fusion ( integrative-microbiomics.ntu.edu.sg ). Patients at greatest risk of exacerbation have less complex microbial co-occurrence networks, reduced ersity and a higher degree of antagonistic interactions in their airway microbiome. Furthermore, longitudinal interactome dynamics reveals microbial antagonism during exacerbation, which resolves following treatment in an otherwise stable multi-biome. Assessment of the Pseudomonas interactome shows that interaction networks, rather than abundance alone, are associated with exacerbation risk, and that incorporation of microbial interaction data improves clinical prediction models. Shotgun metagenomic sequencing of an independent cohort validated the multi-biome interactions detected in targeted analysis and confirmed the association with exacerbation. Integrative microbiomics captures microbial interactions to determine exacerbation risk, which cannot be appreciated by the study of a single microbial group. Antibiotic strategies probably target the interaction networks rather than in idual microbes, providing a fresh approach to the understanding of respiratory infection.
Publisher: Elsevier BV
Date: 08-2020
Publisher: Informa UK Limited
Date: 23-05-2017
DOI: 10.1080/23744235.2017.1330553
Abstract: The Rangipo strain of Mycobacterium tuberculosis achieved notoriety in New Zealand due to its role in several tuberculosis (TB) outbreaks. Why this strain should be the source of relatively large clusters of the disease is unknown. In this work, we performed an in-depth analysis of the genome of the Rangipo strain to determine whether it offers clues to understanding its prevalence. Next-generation sequencing was performed on nine isolates which matched the Rangipo genotypic profile. Sequence reads were assembled against the H37Rv reference genome and single-locus variants identified. Unmapped reads were compared against the genome sequences of other M. tuberculosis strains, in particular CDC1551, Haarlem and Erdman. Across the nine Rangipo strains, a total of 727 single-locus variants were identified with respect to H37Rv, of which 700 were common to all Rangipo strains sequenced. Within the common variants, 386 were non-synonymous, with 12 occurring in genes associated with M. tuberculosis virulence. Next-generation and Sanger sequencing determined the presence of three genes in the Rangipo isolates, which are absent in H37Rv, but which have been reported to be important for the pathogenicity of M. tuberculosis. The differentially encoded Rangipo genes consisted of transcriptional regulator EmbR2, and molybdopterin cofactor biosynthesis proteins A and B. The Rangipo strain also harbours an extended DNA helicase and an additional adenylate cyclase. Our study provides new insights into the genomic content of the New Zealand Rangipo strain of M. tuberculosis and highlights the presence of additional virulence-related loci not found in H37Rv.
Publisher: American Society for Microbiology
Date: 22-12-2020
Publisher: Elsevier BV
Date: 05-2010
DOI: 10.1016/J.DIAGMICROBIO.2009.12.017
Abstract: This study sought to identify mechanisms behind resistance to third-generation cephalosporins and ciprofloxacin in Irish multidrug-resistant Enterobacteriaceae isolates. The most prevalent extended-spectrum beta-lactamase genes identified were bla SHV-12 and bla CTX-M-15. These were associated with the fluoroquinolone resistance genes aac(6')-IB-cr, qnrA and qnrB, not previously reported in Irish isolates.
Publisher: AMPCo
Date: 21-02-2019
DOI: 10.5694/MJA2.50044
Publisher: Public Library of Science (PLoS)
Date: 26-11-2019
Publisher: Microbiology Society
Date: 10-2012
Abstract: PyeR (PA4354) is a novel member of the ArsR family of transcriptional regulators and modulates biofilm formation in Pseudomonas aeruginosa. Characterization of this regulator showed that it has negative autoregulatory properties and binds to a palindromic motif conserved among PyeR orthologues. These characteristics are in line with classical ArsR-family regulators, as is the fact that PyeR is part of an operon structure (pyeR-pyeM-xenB). However, PyeR also exhibits some atypical features in comparison with classical members of the ArsR family, as it does not harbour metal-binding motifs and does not appear to be involved in metal perception or resistance. Hence, PyeR belongs to a subgroup of non-classical ArsR-family regulators and is the second ArsR regulator shown to be involved in biofilm formation.
Publisher: American Thoracic Society
Date: 08-2020
Publisher: Public Library of Science (PLoS)
Date: 21-02-2018
Publisher: American Society for Microbiology
Date: 07-2012
DOI: 10.1128/JB.06632-11
Abstract: MexT is a global LysR transcriptional regulator known to modulate antibiotic resistance and virulence in Pseudomonas aeruginosa . In this study, a novel role for MexT in mediating intrinsic disulfide stress resistance was demonstrated, representing the first identified phenotype associated with inactivation of this regulator in wild-type cells. Disruption of mexT resulted in increased susceptibility to the disulfide stress elicitor diamide [diazenedicarboxylic acid bis( N , N ,-di-methylamide)]. This compound is known to elicit a specific stress response via depletion of reduced glutathione and alteration of the cellular redox environment, implicating MexT in redox control. In support of this, MexT-regulated targets, including the MexEF-OprN multidrug efflux system, were induced by subinhibitory concentrations of diamide. A mexF insertion mutant also exhibited increased diamide susceptibility, implicating the MexEF-OprN efflux system in MexT-associated disulfide stress resistance. Purified MexT protein was observed to form an oligomeric complex in the presence of oxidized glutathione, with a calculated redox potential of −189 mV. This value far exceeds the thiol-disulfide redox potential of the bacterial cytoplasm, ensuring that MexT remains reduced under normal physiological conditions. MexT is activated by mutational disruption of the predicted quinone oxidoreductase encoded by mexS . Alterations in the cellular redox state were observed in a mexS mutant (PA14 nfxC ), supporting a model whereby the perception of MexS-associated redox signals by MexT leads to the induction of the MexEF-OprN efflux system, which, in turn, may mediate disulfide stress resistance via efflux of electrophilic compounds.
Publisher: Springer Science and Business Media LLC
Date: 2020
Publisher: American Society for Microbiology
Date: 27-10-2020
Abstract: Molecular mechanisms by which sex steroids interact with P. aeruginosa to modulate its virulence have yet to be reported. Our work provides the first characterization of a steroid-induced membrane stress mechanism promoting P. aeruginosa virulence, which includes the release of proinflammatory outer membrane vesicles, resulting in inflammation, host tissue damage, and reduced bacterial clearance. We further demonstrate that at nanomolar (physiological) concentrations, male and female sex steroids promote virulence in clinical strains of P. aeruginosa based on their dynamic membrane fluidic properties. This work provides, for the first-time, mechanistic insight to better understand and predict the P. aeruginosa related response to sex steroids and explain the interin idual patient variability observed in respiratory diseases such as cystic fibrosis that are complicated by gender differences and chronic P. aeruginosa infection.
Publisher: Wiley
Date: 25-03-2017
DOI: 10.1111/RESP.13032
Publisher: Oxford University Press (OUP)
Date: 21-10-2009
DOI: 10.1093/NAR/GKP828
Publisher: Elsevier BV
Date: 07-2020
Publisher: Elsevier BV
Date: 10-2009
DOI: 10.1016/J.MICPATH.2009.08.003
Abstract: In the human pathogen Pseudomonas aeruginosa, the LysR-family regulator MexT modulates the induction of the tripartite MexEF-OprN resistance nodulation- ision multi-drug efflux system resulting in increased resistance to erse antibiotics. The MexEF-OprN system is normally quiescent in wild-type cells, but is highly induced in nfxC-type phenotypic mutants in a MexT dependent manner. In addition to antibiotic resistance, induction of mexEF-oprN in nfxC-type mutants has been linked to reduced levels of homoserine lactone-dependent virulence traits, including pyocyanin, elastase, rhamnolipids and PQS and to reduced expression of type three secretion effector proteins. In this study, MexT is overexpressed in wild-type PAO1 and an isogenic mexEF deletion mutant to determine if MexT regulates erse virulence phenotypes dependent or independent of MexEF-OprN. It is shown that MexT regulates type three secretion, pyocyanin production and early surface attachment independent of MexEF-OprN. In contrast, MexT modulation of the expression of the virulence genes rhlA, lasB and hcnB is dependent on MexEF-OprN, which apparently mediates these effects via efflux of cell-signaling intermediates. The data presented demonstrates that MexT may play a more global role in modulating P. aeruginosa virulence than previously reported and suggests that MexT regulates erse targets that mediate phenotypic alterations independent of MexEF-OprN.
Publisher: European Respiratory Society (ERS)
Date: 27-04-2020
DOI: 10.1183/13993003.00418-2020
Abstract: Allergic sensitisation to fungi such as Aspergillus are associated to poor clinical outcomes in asthma, bronchiectasis and cystic fibrosis however, clinical relevance in COPD remains unclear. Patients with stable COPD (n=446) and nondiseased controls (n=51) were prospectively recruited across three countries (Singapore, Malaysia and Hong Kong) and screened against a comprehensive allergen panel including house dust mites, pollens, cockroach and fungi. For the first time, using a metagenomics approach, we assessed outdoor and indoor environmental allergen exposure in COPD. We identified key fungi in outdoor air and developed specific-IgE assays against the top culturable fungi, linking sensitisation responses to COPD outcomes. Indoor air and surface allergens were prospectively evaluated by metagenomics in the homes of 11 COPD patients and linked to clinical outcome. High frequencies of sensitisation to a broad range of allergens occur in COPD. Fungal sensitisation associates with frequent exacerbations, and unsupervised clustering reveals a “highly sensitised fungal predominant” subgroup demonstrating significant symptomatology, frequent exacerbations and poor lung function. Outdoor and indoor environments serve as important reservoirs of fungal allergen exposure in COPD and promote a sensitisation response to outdoor air fungi. Indoor (home) environments with high fungal allergens associate with greater COPD symptoms and poorer lung function, illustrating the importance of environmental exposures on clinical outcomes in COPD. Fungal sensitisation is prevalent in COPD and associates with frequent exacerbations representing a potential treatable trait. Outdoor and indoor (home) environments represent a key source of fungal allergen exposure, amenable to intervention, in “sensitised” COPD.
Publisher: Elsevier BV
Date: 07-2012
No related grants have been discovered for Micheál Mac Aogáin.